Summary

Myxoedema coma is a severe form of hypothyroidism with multiple organ dysfunction, characterised by an altered state of consciousness and hypothermia. Intravenous thyroid hormone replacement therapy is the preferred treatment for myxoedema. The mortality rate associated with this disease is high, and early detection and intervention are essential. Supraglottal myxoedema is a rare form of periglottic oedema and can be fatal. A previously healthy 66-year-old man presented with impaired consciousness, hypothermia, and nonpitting oedema. Blood tests revealed the presence of hypothyroidism and respiratory acidosis. He was intubated for type 2 respiratory failure; however, severe laryngeal oedema made the procedure difficult to perform. Oral thyroid hormone therapy was initiated under the diagnosis of myxoedema coma. Tracheostomy was performed because of prolonged type 2 respiratory failure and laryngeal oedema. Three weeks after admission, the patient was weaned off the ventilator. Approximately a week later, laryngeal oedema improved, and the tracheostomy tube was removed. The patient was discharged and remained stable for 3 months. This case report describes a patient with comatose myxoedema and supraglottic oedema who was successfully treated with oral medication alone. This case shows that supraglottic oedema should be considered even in the absence of wheezing or other signs of upper airway obstruction.

Learning points

• Myxoedema coma is a differential diagnosis of respiratory acidosis.

• In myxoedematous coma, the possibility of difficult intubation due to supraglottic oedema should be considered.

• Tracheostomy should be considered for supraglottic myxoedema, which often results in prolonged ventilator use.

• Supraglottic myxoedema can be treated with oral medications.

Summary

IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function.

Learning points

• Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis.

• In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed.

• IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely.

• When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.

Summary

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery.

Learning points

• Insulinoma occasionally leads to postprandial hypoglycemia.

• The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection.

• The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Summary

Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/trisdecanoin) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (¹H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on ¹H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using ¹H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy.

Learning points

• Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride accumulation in the myocardium and coronary arteries, caused by genetic or acquired dysfunction of adipose triglyceride lipase.

• Japan TGCV Study Group developed a specific treatment for idiopathic TGCV using CNT-01 (tricaprin/trisdecanoin), a type of medium-chain fatty acid.

• CNT-01 corrected myocardial lipolysis and reduced TG content in idiopathic TGCV using proton magnetic resonance spectroscopy, which may be a useful noninvasive evaluation of therapeutic efficacy.

Summary

A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 μU/mL; 60 min: 953 μU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother’s diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years.

Learning points

• Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance.

• Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed.

• Clinical courses may differ even if the same genetic mutation is found in a family.

Summary

Fulminant type 1 diabetes (FT1D) is a subtype of diabetes characterized by rapid progression of β-cell destruction, hyperglycemia, and diabetic ketoacidosis (DKA). The pathogenesis of this disease remains unclear. However, viral infections, HLA genes, and immune checkpoint inhibitor use were reportedly involved in this disease. A 51-year-old Japanese man with no chronic medical condition was admitted to our hospital with complaints of nausea and vomiting. Cough, sore throat, nasal discharge, and diarrhea were not noted. He had a medical history of at least two influenza infections. His vaccination history was notable for receiving an inactive split influenza vaccine 12 days prior to developing these symptoms. He was diagnosed with DKA associated with FT1D. His HLA class II genotypes were nonsusceptible to FT1D, and he had a negative history of immune checkpoint inhibitor use. The destruction of the pancreas by cytotoxic T cells is reported to be involved in FT1D. Inactive split influenza vaccines do not directly activate cytotoxic T cells. However, these could activate the redifferentiation of memory CD8-positive T cells into cytotoxic T cells and induce FT1D, as this patient had a history of influenza infections.

Learning points

• Influenza split vaccination could cause fulminant type 1 diabetes (FT1D).

• The mechanism of influenza split vaccine-induced FT1D might be through the redifferentiation of CD8-positive memory T cells into cytotoxic T cells.

Summary

A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. On computed tomography scan, the mass appeared to localize within the tip of the lateral limb of the left adrenal gland, and between the left adrenal gland and the posterior wall of the stomach. The plasma corticotropin and cortisol concentrations and the 24-h urine fractionated metanephrine levels were normal. ¹²³I-metaiodobenzylguanidine scintigraphy showed tumor avidity consistent with a hormonally inactive pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal computed tomography postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a gastrointestinal stromal tumor. Clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathological analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies.

Learning points

• Anatomic structures and tumors that develop in neighboring tissues to the adrenal glands may be confused with primary adrenal tumors.

• ¹²³I- metaiodobenzylguanidine (MIBG) scintigraphy is specific for diagnosing pheochromocytomas and paragangliomas; however, it has been reported that ¹²³I-MIBG may accumulate in neuroendocrine tumors as well as other tumors.

• Clinicians should recognize the limitations of imaging studies and the uncertainty of an imaging-based preoperative diagnosis.

Summary

Prader–Willi syndrome (PWS) is a genetic imprinting disorder that is characterized by obesity, short stature, and hypogonadism. Hypogonadism is characterized by normal luteinizing hormone (LH), high follicle-stimulating hormone (FSH), low testosterone, low inhibin B, and relatively low anti-Müllerian hormone (AMH). Only a few cases of central precocious puberty (CPP) have been reported in PWS, and follow-up for CPP with PWS is not established. Hence, we present a boy with PWS accompanied by CPP. Gonadotropin-releasing hormone analog (GnRHa) therapy was started at 7 years of age, CPP was adequately arrested, and GnRHa therapy was discontinued at 11.3 years of age. Growth hormone (GH) therapy was started at 12 years of age due to inadequate growth. He grew close to his final height, and his testes developed with normal LH, increased FSH, normal testosterone, and reduced AMH corresponding to puberty at 13.5 years of age. The features of 16 patients with PWS with CPP, including our patient, were summarized. Out of seven male patients, five were treated with GnRHa, as well as four out of nine female patients. Out of 16 patients, 6 were assessed with pubertal development over 13 years of age. Pubertal development was considered to be restored in four patients who had GnRHa therapy discontinuation. We should carefully follow-up on pubertal development in CPP. GnRHa therapy is useful for adequate puberty blockage, and pubertal development could be restored with GnRHa therapy discontinuation.

Learning points

• Pubertal development in Prader–Willi syndrome (PWS) varies from hypogonadism to precocious puberty.

• Pubertal development assessment based on clinical features and hormone levels is needed in central precocious puberty (CPP) treatment with PWS.

• Gonadotropin-releasing hormone analog (GnRHa) therapy is useful for CPP with PWS, and pubertal development can be restored with GnRHa therapy discontinuation.

Summary

We report a 26-year-old Japanese man who visited our outpatient clinic presenting fever immediately after i.m. injection of the second dose of a coronavirus disease 2019 (COVID-19) vaccine (Moderna®). At the first visit, the patient had a fever of 37.7°C and a swollen thyroid gland with mild tenderness. He was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free tri-iodothyronine, 32.3 pg/mL; free thyroxine, >7.77 ng/dL; and thyroid-stimulating hormone (TSH) < 0.01 μIU/mL), high C-reactive protein level (7.40 mg/dL), negative TSH receptor antibody, and characteristic ultrasound findings. His HLA types were A*02:01/24:02, B*15:11/35:01, Cw*03:03, DRB1*09:01/12:01, DQB1*03:03, and DPB1*05: 01/41:01. He was initially administered prednisolone 15 mg/day, following which the fever subsided. After 10 days, he developed limb weakness and could not walk. The serum potassium level decreased to 1.8 mEq/L, which confirmed the diagnosis of thyrotoxic periodic paralysis (TPP). Potassium supplementation was initiated. The muscle weakness gradually decreased. Prednisolone therapy was terminated 6 weeks after the first visit. His thyroid function returned to normal 5 months after the first visit, through a hypothyroid state. To our knowledge, this is the first reported case of TPP-associated SAT following COVID-19 vaccination. Persistent fever following vaccination should be suspected of SAT. Additionally, TPP may be associated with SAT in Asian male patients.

Learning points

• Following coronavirus disease 2019 (COVID-19) vaccination, subacute thyroiditis may develop regardless of the vaccine type.

• If persistent fever, anterior neck pain, swelling and tenderness of thyroid gland, and symptoms of thyrotoxicosis are observed immediately after the COVID-19 vaccination, examination in consideration of the onset of subacute thyroiditis is recommended.

• HLA-B35 may be associated with the onset of subacute thyroiditis after the COVID-19 vaccination.

• Although rare, subacute thyroiditis can be associated with thyrotoxic periodic paralysis, especially in Asian men.

• Glucocorticoid therapy for subacute thyroiditis may induce thyrotoxic periodic paralysis through hypokalemia.

Summary

We encountered a case of childhood-onset lymphocytic infundibuloneurohypophysitis, based on the MRI and endocrinological findings, with decreased function of the anterior and posterior lobes of the pituitary. Three years after the diagnosis, the patient developed non-alcoholic steatohepatitis (NASH), which was effectively treated by growth hormone (GH) supplementation. The present case demonstrated that NASH can be effectively treated by short-term GH supplementation, even in late childhood.

Learning points

• In recent years, the efficacy of growth hormone replacement therapy in normalizing the liver function of adult-onset growth hormone deficiency patients with non-alcoholic steatohepatitis (NASH) has been reported.

• Lymphocytic infundibuloneurohypophysitis is a very rare disease, particularly in childhood.

• We here presented a rare case of a child with lymphocytic infundibuloneurohypophysitis who developed NASH and showed substantial improvement in liver function after growth hormone treatment.